The unique structural features of teeth and bones appear to have important roles in their resistance to disease. We will evaluate the role of nano-structural characteristics of bone and enamel in providing the nanosize-based resistance to dissolution recently documented for calcium phosphate nanocrystals. Initial contacts between an organic matrix and mineral nuclei are presumed to be crucial for the highly structured mineralization of teeth and bones by being imprinted on the mineral-matrix composite during initial formation events. Moreover, the presence of soluble proteins in bone and tooth mineral and observations of mineral growth in their presence suggest they act as control agents over growth rates and morphologies. Although many in vitro studies have looked at mineralization of collagen and dentin, they have not emphasized the earliest events during which mineral phase, position, morphology and orientation are determined. In particular, almost nothing is known about the pathway of crystallization from solvated ions to final apatitic mineral phase, nor has the potential existence of an amorphous precursor phase been explored. In this project, we will use constant composition, in situ AFM, and molecular modeling to determine the kinetics and energetics of apatite formation on dentin and collagen surfaces at realistic driving forces, determine the evolution of phases, identify the sites of nucleation, and define the structural relationships and stereochemical interactions that govern mineral formation on these matrices. Solid phases will be investigated by high resolution scanning and transmission electron microscopy, EDX, small/wide-angle X-ray scattering, ESCA, SIMS, differential scanning calorimetry, and zeta potential. The effect of important soluble proteins including amelogenin, osteopontin and their potentially functional peptide domains will be investigated.